Hi my name is Anne (but I go by Annie) Kaplan. This autumn I will be a sophomore at the Winsor School in Boston MA. I live in Wellesley MA (very close to the BLI camp).
This year I took Biology and really enjoyed it. I am hoping to pursue AP Biology when the course becomes available to me. In the meantime, I wanted to continue studying it through the summer months. I heard about this course and synthetic biology in general through a friend and I loved the idea. I am very excited to be taking this course and learning more about this field. I hope that what I learn here will give me insight into what aspects of Biology I want to continue pursuing. This year I developed an appreciation for ecology. I am a member of my schools Conserve Our World (COW) club where we discuss environmental issues and potential solutions. However, synthetic biology seems to be completely different (or at least I am yet to find the place where they converge). I am very excited to be taking this course and I hope to get a lot out of it!
Brief introduction/background:
In Sub-Saharan Africa, as well as regions of Asia and South America malaria is thought to be the cause for over hundreds of thousands of deaths per year. Malaria is a parasite transmitted through mosquito saliva when injected into a person. In the year 2015 alone, there were an estimated 214 million cases of malaria and 438,000 deaths of children under five years of age from the disease. However, malaria is treatable. The current method of treating malaria is to have someone infected by the disease take an oral medication such as chloroquine or artemisinin.
The problem at hand:
Although there are medications to treat and even cure malaria, there are major issued regarding A. Accessibility, B. Quantity, and C. Price.
A. Accessibility- As stated in the "Brief introduction" section, the places where malaria is found are Sub-Saharan Africa, Asia, and South America. Unfortunately, in all of these places (and especially in Africa where 90% of malaria deaths occur) there is not frequent access to medical care and clinics where one could be treated for malaria. With an increase in accessibility to proper medication malaria deaths have declined by 30%; therefore it is proven that with more accessibility to treatment there is potential for the rate of people infected by the parasite to plummet.
B. Quantity- With such a high number of people contracting malaria there
is not necessarily enough of a medicine to go around. It is likely that there could even be no medicine at a given point in a clinic; regardless of whether a medical facility is accessible to somebody the issue regarding quantity of treatments is also a factor of high death rates from malaria.
C. Price- In Africa, people are often living under a dollar a day. With conditions like that, being able to afford vaccinations and treatments is often out of the question for many. The fact that the only treatments available to the people in Sub-Saharen Africa are medications which require purchasing and repurchasing also factor into the widespread of malaria.
Competing technologies and why they do not work:
Currently, there is an effort to increase the amount and quality of treatments for malaria. For example, The Bill and Melinda Gates Foundation is working to eradicate malaria by advancing the drug artemisinin and increasing it's quantity in clinics in Africa. Ideally this would be a viable solution, but in actuality the method does not fully address any of the three major areas of problem. A. Although there would be more of the drug in circulation it is still hard for many people living in the desolate regions where malaria is common to be able to go to the clinics where artemisinin drugs are. B. Even though there would be more of the drug in production it is likely that it would still not be enough to treat the 214 million cases of malaria. C. According to the Gates Foundation website this "multi-year ongoing project" has already costed 2 billion dollars and continues to need funding. Although the people affected by malaria are not paying for this funding, the amount of money needed for the project makes it unreliable.
Please note: I personally admire the work that the Bill and Melinda Gates foundation is doing even though the paragraph above was quite harsh. I do not mean to disrespect the foundation and what it has done to battle malaria.
My design:
My design uses CRISPR/Cas9 technology to solve the problems at hand. The goal with this design is to have a constant influx of antibodies against malaria called anti-plasmodium falciparum antibody.
In this design I use CRISPR/Cas9 to insert a gene which enables the cells of mosquitos to produce an anti-plasmodium falciparum antibody (an antibody against the most deadly strain of malaria). If the gene is inserted into a hyper variable region of DNA than it would successfully do it's job of producing the antibody without disturbing any of the other vital genes that the mosquito needs to live.
Also, in order to do this I would also need to include a constitutive promoter and a gene drive.
Constitutive promoter: By adding a constitutive promoter it is ensuring that the gene is turned on at all times and there is a dramatic influx in the amount of antibodies to fight the disease.
Gene drive: The addition of a gene drive ensures that the anti-plasmodium falciparum antibody will be passed down from the original generation to the generations to follow. Although it is not possible to give every mosquito the inserted genes, by adding a gene drive it increases the amount the gene is passed down.
Then, in the design below, the modified gene being converted into the antibody is displayed. Once the antibodies are secreted the final plan for the project can be executed.
The final plan:
If all goes according to research then what should happen is the antibodies are produced by the mosquito in abundance. The fact that the mosquito immune system is so primitive would mean that it could not attack the foreign protein. Instead, the antibody will be present in the mosquito to make their plasmodium falciparum parasite (if they have it) no longer a vicious malady. There are two possible case scenarios from here: either the antibody and antigen will latch whilst in the mosquito; if one is bitten by the mosquito they would never actually contract a deadly version of malaria. Or, when the mosquito injects it's saliva into a person the mosquito would be passing on the antibodies to fight the disease as well as the live parasite. Both scenarios still make for Malaria to not at all hinder the person being bitten by the mosquito.
Expected results:
This truth table depicts how by having the antibody in production would lead to a lack of active malaria in the mosquito and ostensibly other animals bitten by mosquitos. These results are the solution to the problem of the malaria spread through Africa, Asia, and South America
Advantages:
Unlike other technologies on the market this design addresses all three of the problems at hand.
Accessibility: if malaria is spreading through something that is as common as a mosquito, the treatment to malaria must be equally accessibly. Putting the treatment for malaria in the actual mosquito clearly addresses this necessity. In fact, because not every mosquito carries malaria after generations of the gene being passed down it is even possible that the treatment would be more accessibly to people then the disease itself.
Quantity: similar to accessibility, because a the generations of a mosquito are so short (roughly 40 days) the amount of mosquitos with this gene will multiply rapidly and the treatment will become abundant -again, potentially even more abundant than malaria itself.
Price: Although engineering the mosquito has the potential to be expensive, the best part of the design is that the mosquito is the vendor for the treatment, not people with oral medications. What this means is that nobody has to pay money to buy medication or hire nurses to administer vaccinations. As a result, once the mosquito has been engineered the antibody will be free of charge for all those in need.
Potential problems:
The main problem with this design is that does not cater to every strain of malaria. The whole system is reliant on the anti-plasmodium falciparum antibody fitting with the plasmodium falciparum parasite, but there are other malaria parasites present which affect humans. The fact that the plasmodium falciparum parasite is the most deadly makes the entire project worthwhile, but if at some point in the future the strain evolves or another one becomes more prominent and the current antibody no longer fits there could be a potential problem.
Testing:
The only proper way to test this experiment is to try it out! To test the design one would use CRISPR/Cas9 to insert the gene which codes for anti-plasmodium falciparum antibody (ideally the gene drive as well, but that is not as necessary in the testing phase). Then, the mosquito could bite a rodent/animal of sorts and and ELISA test could be conducted to see if there was an increase in antibodies in the animal. If the results of the ELISA test show an increase in antibodies then it is revealed that the design works and could potentially be used out of the laboratory.
Hi my name is Anne (but I go by Annie) Kaplan. This autumn I will be a sophomore at the Winsor School in Boston MA. I live in Wellesley MA (very close to the BLI camp).
This year I took Biology and really enjoyed it. I am hoping to pursue AP Biology when the course becomes available to me. In the meantime, I wanted to continue studying it through the summer months. I heard about this course and synthetic biology in general through a friend and I loved the idea. I am very excited to be taking this course and learning more about this field. I hope that what I learn here will give me insight into what aspects of Biology I want to continue pursuing. This year I developed an appreciation for ecology. I am a member of my schools Conserve Our World (COW) club where we discuss environmental issues and potential solutions. However, synthetic biology seems to be completely different (or at least I am yet to find the place where they converge). I am very excited to be taking this course and I hope to get a lot out of it!
Design: Genetically Modified Mosquitos
Brief introduction/background:
In Sub-Saharan Africa, as well as regions of Asia and South America malaria is thought to be the cause for over hundreds of thousands of deaths per year. Malaria is a parasite transmitted through mosquito saliva when injected into a person. In the year 2015 alone, there were an estimated 214 million cases of malaria and 438,000 deaths of children under five years of age from the disease. However, malaria is treatable. The current method of treating malaria is to have someone infected by the disease take an oral medication such as chloroquine or artemisinin.
The problem at hand:
Although there are medications to treat and even cure malaria, there are major issued regarding A. Accessibility, B. Quantity, and C. Price.
A. Accessibility- As stated in the "Brief introduction" section, the places where malaria is found are Sub-Saharan Africa, Asia, and South America. Unfortunately, in all of these places (and especially in Africa where 90% of malaria deaths occur) there is not frequent access to medical care and clinics where one could be treated for malaria. With an increase in accessibility to proper medication malaria deaths have declined by 30%; therefore it is proven that with more accessibility to treatment there is potential for the rate of people infected by the parasite to plummet.
B. Quantity- With such a high number of people contracting malaria there
is not necessarily enough of a medicine to go around. It is likely that there could even be no medicine at a given point in a clinic; regardless of whether a medical facility is accessible to somebody the issue regarding quantity of treatments is also a factor of high death rates from malaria.
C. Price- In Africa, people are often living under a dollar a day. With conditions like that, being able to afford vaccinations and treatments is often out of the question for many. The fact that the only treatments available to the people in Sub-Saharen Africa are medications which require purchasing and repurchasing also factor into the widespread of malaria.
Competing technologies and why they do not work:
Currently, there is an effort to increase the amount and quality of treatments for malaria. For example, The Bill and Melinda Gates Foundation is working to eradicate malaria by advancing the drug artemisinin and increasing it's quantity in clinics in Africa. Ideally this would be a viable solution, but in actuality the method does not fully address any of the three major areas of problem. A. Although there would be more of the drug in circulation it is still hard for many people living in the desolate regions where malaria is common to be able to go to the clinics where artemisinin drugs are. B. Even though there would be more of the drug in production it is likely that it would still not be enough to treat the 214 million cases of malaria. C. According to the Gates Foundation website this "multi-year ongoing project" has already costed 2 billion dollars and continues to need funding. Although the people affected by malaria are not paying for this funding, the amount of money needed for the project makes it unreliable.
Please note: I personally admire the work that the Bill and Melinda Gates foundation is doing even though the paragraph above was quite harsh. I do not mean to disrespect the foundation and what it has done to battle malaria.
My design:
My design uses CRISPR/Cas9 technology to solve the problems at hand. The goal with this design is to have a constant influx of antibodies against malaria called anti-plasmodium falciparum antibody.
In this design I use CRISPR/Cas9 to insert a gene which enables the cells of mosquitos to produce an anti-plasmodium falciparum antibody (an antibody against the most deadly strain of malaria). If the gene is inserted into a hyper variable region of DNA than it would successfully do it's job of producing the antibody without disturbing any of the other vital genes that the mosquito needs to live.
Also, in order to do this I would also need to include a constitutive promoter and a gene drive.
Constitutive promoter: By adding a constitutive promoter it is ensuring that the gene is turned on at all times and there is a dramatic influx in the amount of antibodies to fight the disease.
Gene drive: The addition of a gene drive ensures that the anti-plasmodium falciparum antibody will be passed down from the original generation to the generations to follow. Although it is not possible to give every mosquito the inserted genes, by adding a gene drive it increases the amount the gene is passed down.
Then, in the design below, the modified gene being converted into the antibody is displayed. Once the antibodies are secreted the final plan for the project can be executed.
The final plan:
If all goes according to research then what should happen is the antibodies are produced by the mosquito in abundance. The fact that the mosquito immune system is so primitive would mean that it could not attack the foreign protein. Instead, the antibody will be present in the mosquito to make their plasmodium falciparum parasite (if they have it) no longer a vicious malady. There are two possible case scenarios from here: either the antibody and antigen will latch whilst in the mosquito; if one is bitten by the mosquito they would never actually contract a deadly version of malaria. Or, when the mosquito injects it's saliva into a person the mosquito would be passing on the antibodies to fight the disease as well as the live parasite. Both scenarios still make for Malaria to not at all hinder the person being bitten by the mosquito.
Expected results:
This truth table depicts how by having the antibody in production would lead to a lack of active malaria in the mosquito and ostensibly other animals bitten by mosquitos. These results are the solution to the problem of the malaria spread through Africa, Asia, and South America
Advantages:
Unlike other technologies on the market this design addresses all three of the problems at hand.
Accessibility: if malaria is spreading through something that is as common as a mosquito, the treatment to malaria must be equally accessibly. Putting the treatment for malaria in the actual mosquito clearly addresses this necessity. In fact, because not every mosquito carries malaria after generations of the gene being passed down it is even possible that the treatment would be more accessibly to people then the disease itself.
Quantity: similar to accessibility, because a the generations of a mosquito are so short (roughly 40 days) the amount of mosquitos with this gene will multiply rapidly and the treatment will become abundant -again, potentially even more abundant than malaria itself.
Price: Although engineering the mosquito has the potential to be expensive, the best part of the design is that the mosquito is the vendor for the treatment, not people with oral medications. What this means is that nobody has to pay money to buy medication or hire nurses to administer vaccinations. As a result, once the mosquito has been engineered the antibody will be free of charge for all those in need.
Potential problems:
The main problem with this design is that does not cater to every strain of malaria. The whole system is reliant on the anti-plasmodium falciparum antibody fitting with the plasmodium falciparum parasite, but there are other malaria parasites present which affect humans. The fact that the plasmodium falciparum parasite is the most deadly makes the entire project worthwhile, but if at some point in the future the strain evolves or another one becomes more prominent and the current antibody no longer fits there could be a potential problem.
Testing:
The only proper way to test this experiment is to try it out! To test the design one would use CRISPR/Cas9 to insert the gene which codes for anti-plasmodium falciparum antibody (ideally the gene drive as well, but that is not as necessary in the testing phase). Then, the mosquito could bite a rodent/animal of sorts and and ELISA test could be conducted to see if there was an increase in antibodies in the animal. If the results of the ELISA test show an increase in antibodies then it is revealed that the design works and could potentially be used out of the laboratory.
Sources:
http://www.mayoclinic.org/diseases-conditions/malaria/diagnosis-treatment/treatment/txc-20168001http://www.gatesfoundation.org/What-We-Do/Global-Health/Malaria
https://www.youtube.com/watch?v=N0iOB0a3Sho
https://en.wikipedia.org/wiki/Conserved_sequencehttp://www.pnas.org/content/91/21/9866.short
http://reason.com/archives/2014/07/25/gene-drives-are-a-great-way-to-play-god
http://www.who.int/malaria/media/world_malaria_report_2014/en/http://www.who.int/intellectualproperty/events/OpenForumGillSamuels.pdf
http://www.biotechrabbit.com/antibody-production-services-and-
oem/monoclonal-antibodies.htmlhttp://www.sciencedirect.com/science/article/pii/S1357272508005098http://www.jhsph.edu/news/news-releases/2012/dimopoulos-antibiodies.htm